|
Have you ever wondered how psychedelics research is conducted in animals? Rodents produce a distinct and reliable behavioural response to psychedelic drugs - the head-twitch - that can be quantified and used to measure the activity of psychedelic drugs in rodents.
In the 1950s and 1960s, researchers observed that after administering LSD, rodents would rapidly move their heads from side to side in a consistent manner. Watch a video of the head-twitch response here - "LSD & The Head Twitch Response" (Hamilton Morris).
The head-twitch response (HTR) has been observed in response to LSD, psilocybin, mescaline, 5-MeO-DMT, DOI, and many other psychedelics. Interestingly, this behavior is rarely seen in response to other classes of drugs and seems to be specific to drugs that activate the serotonin 2A (5-HT2A) receptor (classic psychedelics). The HTR is also dose-dependent, which means the behaviour increases in proportion to the dose of psychedelics administered (see the figure above).
The head-twitch response is now considered to be a reliable measure of the activity of psychedelic drugs in rodents and is widely used in preclinical psychedelic research. It has been extensively studied and validated as a behavioral assessment of the potency and efficacy of psychedelic drugs. Researchers have even developed a fully automated video-software system that automatically scores the behaviour (Fuente Revenga et al., 2019).
As the HTR indicates activity at the 5-HT2A receptor, and probable "psychedelic" activity, it can be used to help identify novel psychedelic drugs. Researchers can then take these new, likely psychedelic compounds, and explore their therapeutic potential for conditions like depression, anxiety, and addictions.
|
|
|
Are you Psylo's next team member?
We are hiring for a Chief of Staff to be located in Colorado.
Details and application here.
|
|
Psychedelic Clinical Research
🍄 Psilocybin Therapy reduces depression in Patients With Cancer | A single dose of psilocybin administered with therapy produced clinically meaningful, rapid, and sustained improvement in symptoms of depression over 8 weeks in patients with cancer who were diagnosed with major depression disorder (N=30). The psilocybin was administered in a 1-to-1 therapist-to-patient ratio to groups of patients (up to 4 patients simultaneously) in a community cancer center. JAMA Oncology
💥 A whole-brain model of the neural entropy increase elicited by psychedelic drugs | One of the most notable neurophysiological markers of psychedelics is increased entropy in spontaneous brain activity. This paper provides the first mechanistic explanation of said increased neural entropy. Entropy changes were not uniform across the brain: entropy increased in all regions, but the larger effect were localised in visuo-occipital regions. Scientific Reports
🧠 The effects of LSD on brain function and connectivity | A novel technique (regression dynamic causal modelling; rDCM) was used to assess brain activity in response to LSD. Stronger interregional connectivity and reduced self-inhibition was observed in certain regions of the brain (not occipital and subcortical regions) with LSD compared to placebo. Observed changes correlated with LSD's subjective effects of LSD and were distinct enough to discriminate whither someone was one LSD or not in a machine learning-based analysis with high accuracy. This neural signature may serve as a potential biomarker of LSD subjective effects. Neuropsychopharmacology
💉 Pharmacokinetics of N,N-dimethyltryptamine (DMT) in Humans | The full pharmacokinetics characterization of DMT following a slow IV infusion in humans confirmed rapid attainment of peak plasma concentrations followed by rapid clearance (N=24). Clearance of DMT was reduced through the inhibition of MAO-A, CYP2D6 and to a lesser extent CYP2C19.
👀 Does Psilocybin to promote synaptogenesis in the brains of patients with mild cognitive impairment. Medical Hypotheses
A Case Series Providing Clinical Evidence that Methylone Produces Rapid and Robust Improvements in Major Depressive Disorder - Front Psychiatry
📈 [Preprint] Psychological and physiological effects of extended DMT | DMT, administered as a continuous intravenous infusion, lasting 30 minutes, was well tolerated (N=11). While blood concentrations of DMT increased consistently during the infusion, the psychological effects plateaued. This suggests the development of acute psychological tolerance to DMT. PsyArXiv
|
|
Psychedelic Preclinical Research
🐭 5-MeO-DMT modifies innate behaviors and promotes structural neural plasticity in mice | The short-acting psychedelic 5-MeO-DMT has been associated with improvement in depression and anxiety symptoms in early phase clinical studies. However, relatively little is known about the behavioral and neural mechanisms of 5-MeO-DMT. In mice, the behavior profile of 5-MeO-DMT was characterized and compared to psilocybin. 5-MeO-DMT produced long-lasting increases in dendritic spine density (a marker of neuroplasticity); however, unlike psilocybin, 5-MeO-DMT did not affect the size of dendritic spines. Neuropsychopharmacology
🧠 Sex-specific effects of psychedelic drug exposure on central amygdala reactivity and behavioral responding | A single dose of psilocin produces sex-specific, time-dependent, and enduring changes in activity in a region of the brain implicated in affective psychiatric disorder (central amygdala) and behavioral responding to specific components of an aversive stimulus. Translational Psychiatry
🐟 [Preprint] High-resolution tracking of unconfined zebrafish behavior reveals stimulatory and anxiolytic effects of psilocybin | A behavioral tracking system for larval zebrafish was developed and used to investigate the effects of psilocybin. Machine learning analyses of precise body kinematics identified spontaneous exploration, visually-driven rapid scooting, and stress-induced zigzag swim patterns as behavioral effects of acute psilocybin treatment. BioRxiv
|
|
Psychedelic Research Reviews
- Emerging Challenges for Psychedelic Therapy - JAMA Psychiatry
- Mini-review: The neurobiology of treating substance use disorders with classical psychedelics - Front Neurosci
- Effects of serotonergic psychedelics on mitochondria: Transdiagnostic implications for mitochondria-related pathologies - J Psychopharmacology
|
|
Psychedelic Clinical Trials Update
A round-up of the latest registered clinical trials investigating psychedelics:
- A Trial of GH001 [5-MeO-DMT] in Patients With Treatment-resistant Depression - NCT05800860
- A clinical trial of Psilocybin-assisted psychotherapy as a treatment for anorexia nervosa - ACTRN12623000357651
- Phase 2 Clinical Trial of GH001 [5-MeO-DMT] in Postpartum Depression - NCT05804708
- Dose-finding Study for the Combination of DMT and Harmine in Healthy Subjects (DHTP) - NCT05829603
- Acute Effects of 3,4-methylenedioxymethamphetamine (MDMA) With and Without a Booster Dose - NCT05809271
|
|
Other News
- 🚵♀️ Is there a common path to the psychedelic experience? - Science Daily, 25 April
- A study takes a closer look at the neurobiology of psychedelic experiences caused by nitrous oxide, ketamine and LSD.
- 🌎 US could soon approve MDMA therapy — opening an era of psychedelic medicine - Nature
- Perceptions have shifted dramatically in the past few years on the therapeutic value of illicit drugs such as ecstasy. But questions still linger about what FDA approval might look like.
- 😷 The Latest Promising Long COVID Treatment? Psychedelic Drugs - Time, 17 April
- 💥 The Church of Psilomethoxin: Fantasy Chemistry Gets Fact Checked - Psychedelic Alpha, 17 April
- This month, a preprint publication suggested that the sacrament of the self-styled Church of Psilomethoxin contained not a shred of the elusive compound. Psychedelic researcher and Psylo team member, Mario de la Fuente, interprets this purported fact-checking as an example of self-regulation within the psychedelic space.
- 🩺 The big idea: should doctors be able to prescribe psychedelics? - The Guardian, 10 April
- 😢 A Psychedelics Pioneer Takes the Ultimate Trip - The New York Times, 7 April
- Dr. Roland Griffiths is a pioneer of psychedelics and consciousness research. He has been diagnosed with Stage 4 cancer and in this powerful article he talks about "learning to die."
- 🔍 European ‘shamans’ took psychedelic drugs 3,000 years ago - National Geographic, 7 April
- ⌛ STATEMENT: MAPS-Funded Phase 3 Research Reports Results from Long-Term Observational Follow-Up Study on MDMA-Assisted Therapy for PTSD - MAPS, 5 April
|
|
|
We're expanding into the US! 🚀🌎 CSO, Sam Banister, and Head of Communications, Dilara Bahceci, are heading to Boulder, Colorado to join Psylo’s VP of Translational Research, Lawrence Wennogle, and set up shop in the US. With a robust biotech ecosystem, access to capital, broad market potential, and collaborative opportunities, Psylo is poised for success in advancing novel treatments for depression. More reasons why Colorado is an ideal place for psychedelic biotech here.
|
|
|
CEO, Josh Ismin, and dear friend, Scott Riddle, took to stage for Raising the Bar festival. They discussed the therapeutic potential of psilocybin from psychedelic mushrooms, drug discovery and the future of mental healthcare. The talk was recorded and will be released as a podcast soon. Watch this space 👀
|
|
|
Did you miss the legendary webinar between David Nichols, Charles Nichols and Sam Banister (CSO)? They discussed the origins and future of psychedelics research. Watch the recording here.
|
|
|
|
Josh Ismin will join a a panel of health technology and innovation experts to discuss how we can leverage local resources to overcome the challenges and support an uplift in health technology innovation, 15 May. Register here.
|
|
|
SHARE THIS WITH SOMEONE YOU KNOW
|
|
|
This is Psylo's Psychedelic Science Newsletter, delivering curated research and news right to your inbox. Join the revolution.
|
|
|
